PD-L1 expression, patterns of progression and patient-reported outcomes (PROs) with durvalumab plus platinum-etoposide in ES-SCLC: Results from CASPIAN

Paz‐Ares, Luis; Goldman, Jonathan W.; Garassino, Marina Chiara; Dvorkin, Mikhail; Trukhin, Dmytro; Statsenko, Galina; Hotta, Katsuyuki; Ji, Jun Ho; Hochmair, Maximilian; Войтко, Олександр; Havel, Libor; Poltoratskiy, A.; Losonczy, György; Reinmuth, Niels; Shrestha, Yashaswi; Patel, Nikunj; Mann, Helen; Jiang, Haiyi; Özgüroǧlu, Mustafa; Chen, Y.

doi:10.1093/annonc/mdz394.089

Cited by 49 publications

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“…At a median follow‐up of 14.2 months, the primary endpoint of median OS was significantly improved for durvalumab plus chemotherapy compared with chemotherapy alone (13.0 vs. 10.3 months; HR, 0.73; 95% CI, 0.59─0.91; p = .005), and both PFS and ORR were comparable (Table 1) [40]. Global health status (measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core‐30) also favored durvalumab plus chemotherapy compared with chemotherapy alone (HR, 0.81; 95% CI, 0.63─1.05) [51]. At a longer median follow‐up of 25.1 months the OS benefit was maintained (12.9 vs. 10.5 months; HR, 0.75; 95% CI, 0.62─0.91; p = .0032), and both PFS and ORR remained comparable [52].…”

Section: Resultsmentioning

confidence: 99%

“…Although ICI survival benefits emerged between 6 and 7 months with curves remaining separate at a median follow‐up of approximately 20 months in all trials [48, 50, 52], the survival benefit reached statistical significance for IMpower 133 and CASPIAN [50, 52] and was narrowly missed for KEYNOTE‐604 ( p = .016, OS superiority threshold p = .0128) [48]. ICI plus chemotherapy combinations improved HRQoL in IMpower 133 [49] and CASPIAN [51], although HRQoL data were not available for KEYNOTE‐604 [48]. Although caution should be exercised when considering cross‐trial comparisons, OS differences might be explained by a greater proportion of patients with poor prognosis enrolled in KEYNOTE‐604 as evidenced by the lower median OS for the control arm of this trial compared with IMpower 133 and CASPIAN (9.7 vs. 10.3 and 10.5 months, respectively) [48, 50, 52].…”

Section: Discussionmentioning

confidence: 99%

“…IMpower 133 did not screen for PD‐L1 due to the expected high rate of inadequate sample types (e.g., fine‐needle aspirates, bronchoscopy findings), the low prevalence of PD‐L1 expression on tumor cells, and the lack of association between response and PD‐L1 expression in the phase Ia trial of atezolizumab in SCLC [37, 60]. Although CASPIAN performed a subgroup analysis based on PD‐L1 status, only 51.6% of patients were PD‐L1 evaluable, and no significant interaction was observed with OS based on PD‐L1 expression as a continuous variable (tumor cell, p = .54 and immune cell, p = .23) [51]. A majority of patients (79.5%) in KEYNOTE‐604 were retrospectively evaluable for PD‐L1 status using the combined positive score, and a similar benefit was seen in patients with PD‐L1 expression ≥1 (51.4%) and in those with <1 PD‐L1 expression (48.6%), confirming that PD‐L1 status is not predictive in ES‐SCLC [48].…”

Section: Discussionmentioning

confidence: 99%

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Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

et al. 2020

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Background Small cell lung cancer (SCLC) represents approximately 15% of lung cancers, and approximately 70% are diagnosed as extensive‐stage SCLC (ES‐SCLC). Although ES‐SCLC is highly responsive to chemotherapy, patients typically progress rapidly, and there is an urgent need for new therapies. Immune checkpoint inhibitors (ICIs) have recently been investigated in SCLC, and this review provides guidance on the use of these agents in ES‐SCLC based on phase III evidence. Methods Published and presented literature on phase III data addressing use of ICIs in ES‐SCLC was identified using the key search terms “small cell lung cancer” AND “checkpoint inhibitors” (OR respective aliases). Directed searches of eligible studies were periodically performed to ensure capture of the most recent data. Results Six phase III trials were identified, with four assessing the benefits of ICIs plus chemotherapy first‐line, one evaluating ICIs as first‐line therapy maintenance, and one assessing ICI monotherapy after progression on platinum‐based chemotherapy. The addition of ipilimumab or tremelimumab to first‐line treatment or as first‐line maintenance did not improve survival. Two out of three studies combining PD‐1/PD‐L1 inhibitors with first‐line platinum‐based chemotherapy demonstrated significant long‐lasting survival benefits and improved quality of life with no unexpected safety concerns. PD‐1/PD‐L1 inhibitors as first‐line maintenance or in later lines of therapy did not improve survival. Biomarker research is ongoing as well as research into the role of ICIs in combination with radiation therapy in limited‐stage SCLC. Conclusion The addition of atezolizumab or durvalumab to first‐line platinum‐based chemotherapy for ES‐SCLC prolongs survival and improves quality of life. Implications for Practice Platinum‐based chemotherapy has been standard of care for extensive‐stage small cell lung cancer (ES‐SCLC) for more than a decade. Six recent phase III trials investigating immune checkpoint inhibitors (ICIs) have clarified the role of these agents in this setting. Although ICIs were assessed first‐line, as first‐line maintenance, and in later lines of therapy, the additions of atezolizumab or durvalumab to first‐line platinum‐based chemotherapy were the only interventions that significantly improved overall survival and increased quality of life. These combinations should therefore be considered standard therapy for first‐line ES‐SCLC. Biomarker research and investigations into the role of ICIs for limited‐stage disease are ongoing.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

et al. 2020

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“…Similar results were seen with PD-L1 expression analyses in CASPIAN. 45 In that study, 52% of samples were evaluable: 96% were PD-L1 negative based on tumor-cell expression and 78% were PD-L1 negative based on immune-cell expression. Again, whether PD-L1 expression on tumor cells or immune cells was analyzed, outcomes favored the addition of durvalumab for both PD-L1 positive and negative tumors.…”

Section: Biomarkers For Chemo-immunotherapy In Sclcmentioning

confidence: 94%

Chemo-immunotherapy as first-line treatment for small-cell lung cancer

Farid

Liu

2020

Ther Adv Med Oncol

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Small-cell lung cancer (SCLC) is a highly lethal subtype of lung cancer. Despite concerted efforts over the past several decades, there have been limited therapeutic advances. Traditional chemotherapy offers a high response rate and rapid symptomatic improvement, but its benefit is fleeting, and relapse is quick and unforgiving. Immunotherapy has delivered improved outcomes for patients with many cancers and there was compelling rationale for development in SCLC. While initial efforts with cytotoxic T-lymphocyte protein-4 inhibitors failed to improve upon chemotherapy alone, the addition of programmed death ligand-1 (PD-L1) inhibitors to first-line chemotherapy finally provided long-awaited gains in survival. Atezolizumab, when added to carboplatin and etoposide, improved both progression-free survival and overall survival. Durvalumab, when added to platinum plus etoposide, similarly improved OS. Biomarker development has stalled as PD-L1 expression and tumor mutational burden have not been useful predictive biomarkers. However, based on the significant survival improvements, both atezolizumab and durvalumab were approved by the US Food and Drug Administration to be given with first-line chemotherapy, and these regimens represent the new standards of care for SCLC.

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“…Notably, CASPIAN was an open-label study and responses were investigator-assessed, which may be a possible explanation for the higher ORR. Updated findings presented at the 2019 ESMO annual meeting 29 demonstrated that patients in the durvalumab-PE arm had a lower incidence of new lesions at first progression (41.4% versus 47.2%), whereas progression in target and non-target lesions was similar between arms (42.7% versus 39.4% and 24.6% versus 22.7%). An additional QoL analysis looking at PROs indicated a longer time to deterioration with durvalumab-PE based on favourable HR for all evaluated symptoms.…”

Section: Ici: a First-line Treatmentmentioning

confidence: 97%

First-line immune checkpoint inhibitors for extensive stage small-cell lung cancer: clinical developments and future directions

Ortega-Franco

Ackermann²,

Paz‐Ares

et al. 2021

ESMO Open

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PD-L1 expression, patterns of progression and patient-reported outcomes (PROs) with durvalumab plus platinum-etoposide in ES-SCLC: Results from CASPIAN

Cited by 49 publications

References 0 publications

Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

Chemo-immunotherapy as first-line treatment for small-cell lung cancer

First-line immune checkpoint inhibitors for extensive stage small-cell lung cancer: clinical developments and future directions

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